Mast Cell Activation Syndrome: Quantification of Mast Cells Across Conditions Reveals Limited Diagnostic Utility of...

Mast cell enumeration in gastrointestinal biopsies is commonly requested to diagnose mast cell activation syndrome (MCAS) or systemic mastocytosis (SM) with gastrointestinal (GI) involvement. However, mast cell numbers can be elevated in various disorders and quantities do not reflect functional states. A novel measure, the tryptase depletion index (TDI), was recently proposed as a surrogate measure for mediator release and mast cell activation.

To evaluate the diagnostic utility of the TDI and mast cell counts for differentiating between MCAS, SM, and inflammatory disorders in GI biopsies.

GI biopsy samples from patients with SM or MCAS (n = 64), inflammatory disorders (n = 26), and healthy controls (n = 38) were examined. All sections were immunostained for c-Kit/CD117 and tryptase, and mast cells were quantified within the lamina propria. Testing for KIT D816V mutation and CD25 immunohistochemistry were performed for all cases with suspected SM or MCAS.

Infiltrates of atypical, CD25+ mast cells were confirmed in SM. Mast cell numbers were elevated in SM, MCAS, and inflammatory disorders as compared to healthy tissue. The TDI did not differ significantly among the groups, and fluctuations in TDI can be explained by measurement noise from counting performed on subsequent tissue sections. Receiver operating characteristic analysis showed low sensitivity and specificity for TDI or mast cell enumeration in diagnosing MCAS.

While SM can be substantiated with markers such as CD25/CD30 or KIT mutations, counting mast cells appears of limited utility.